STROKE Professor Iqbal Singh OBE FRCP Stroke? ACT FAST National - PowerPoint PPT Presentation

STROKE Professor Iqbal Singh OBE FRCP

Stroke? → ACT FAST National Stroke Strategy QM1, Raising Awareness, QM2 Time is Brain

Clinical presentations of stroke ▪ Acute onset combination of ➢ Face / arm / leg weakness or sensory loss ➢ Loss of co-ordination ➢ Speech disturbance ➢ Visual disturbance ▪ Acute onset does not mean total deficit within seconds ▪ Most TIAs are < 20 minutes

Background Information • Stroke varies • All begin suddenly • ¼ patients do not leave hospital • ⅓ survivors need help every day due to: ➢ Weakness ➢ Speech problems ➢ Swallowing problems ➢ Visual problems ➢ Memory problems • Urgent recognition & stroke unit admission improves recovery

Background Information • Incidence of stroke now higher than that of acute coronary syndromes • For 1 million inhabitants , There will be 2400 strokes per year (1800 first-ever, 600 recurrent or after TIA) Of these – 700 (29%) will die – 600 (25%) will be dependent – 1100 (46%) will be independent

Why collecting six month assessment data is important Collecting information about patient outcomes at six months enables us to look at: changes in functional outcome and place of residence change in AF status and anticoagulation to improve secondary prevention mood and cognition, in particular identification of these areas which were silent symptons when the patient presented acutely. It is one of the CCG Outcomes Indicator Set (OIS) and was mandated in the National Stroke Strategy. By contributing this information to the audit it will for the first time allow us to assess outcomes at six months both nationally and for individual teams. SSNAP Aug-Nov 2016

Causes of Ischaemic Stroke

Carotid Artery Stenosis External Carotid Stenosis at bifurcation of Internal Carotid Common Carotid

Carotid Endarterectomy European carotid trialists collaborative group  European Carotid Surgery Trial (ECST)  North American symptomatic carotid endarterectomy trial I & II(NASCET)   3 RCT’s (symptomatic) – 6143 pts  Severe Stenosis RRR 48% NNT 15

rrhythmia 1 AF is is th the most common su sustained cardiac arr Prevalence in the general population 1 1 – 2% Europeans suffer from AF, including an estimated >6 million 1 1 million in the UK 2 1.4 x Greater risk in men than women (adjusted for age and risk factors) 2,3 ~25% Lifetime risk in those who reach 40 years of age 1 Incidence is projected to grow significantly 4 AF: atrial fibrillation. 1. 1. Camm et al . Eur Heart J 2010;31:2369 – 429; 2. 2. NHS choices. Atrial fibrillation. http://www.nhs.uk/Conditions/Atrial-fibrillation/Pages/Introduction.aspx. Accessed November 2016; 3. Go et al . JAMA 2001;285:2370 – 2375; 4. Savelieva et al. Clin Cardiol 2008;31:55 – 62.

Burden of f AF and rela lated str troke • Estimated annual burden of AF (2008 data) 1 : Total direct cost to NHS £2.2 billion 5.7 million hospital bed days £1.8 billion Non-bed inpatient costs £124 million Outpatient costs £205 million • Also contributing to the burden of AF are 2 : • Indirect costs, for example loss of time in employment • Cost related to co-morbidities of AF, e.g. stroke • Direct costs of all strokes to the NHS in England are estimated at £2.8 billion 3 • AF is responsible for 20% of all strokes 4 • AF-related strokes are more severe 5 • Severe strokes are >3x more costly on average than typical mild strokes 6 AF: atrial fibrillation; NHS: National Health Service. 1. 1. The Office of Health Economics Estimating the direct costs of atrial fibrillation to the NHS in the constituent countries of the UK and at SHA level in England, 2008. Accessed November 2016; 2. 2. Blomstrom Lundqvist et al . Europace 2011;13:ii9 – 12; 3. Quality Standards Programme. NICE cost impact and commissioning assessment: quality standard for stroke. June 2010. https://www.nice.org.uk/guidance/qs2/resources/cost-impact-and-commissioning-assessment-252272845. Accessed November 2016; 4. Marini et al. Stroke 2005;36:1115 – 1119; 5. Jorgensen et al. Stroke 1996;27:1765 – 1769; 6. Szucs and Bramkamp. J Thromb Haemost 2006;4:1180 – 1185.

Effecti tive AF tr treatm tment: t: Estim timati ting th the potential im impact of f in inadequate tr treatm tment 152,000 strokes annually in the UK 1 20% of strokes due to AF 2 30,400 are due to AF RRR of 64% with warfarin vs no treatment 3 19,456 are preventable with warfarin therapy ~66% of eligible patients treated with warfarin 4 – 33% do not receive warfarin treatment ~6,485 strokes may occur annually in the UK as a result of a lack of appropriate treatment AF: atrial fibrillation; RRR: relative risk reduction. 1. 1. Townsend et al. Coronary heart disease statistics 2012 edition. British Heart Foundation. 2012; 2. 2. Marini et al. Stroke 2005;36:1115 – 1119; 3. Hart et al. Ann Intern Med 2007;146:857 – 867; 4. Connolly et al. Circulation 2007;116:449 – 555.

Cli linical pharmacology of f NOACs Apixaban 1,2 Rivaroxaban 1,3 Dabigatran 1,4 Edoxaban 5 Mechanism of Direct factor Xa Direct factor Xa Direct thrombin Direct factor Xa action inhibitor inhibitor inhibitor inhibitor Oral ~50% 80 – 100% ~6.5% ~62% bioavailability No No Pro-drug No Yes Yes (20 mg and Food effect No 15 mg doses need to No No be taken with food) 50% † Renal clearance ~27% ~33 %* 85% *Direct renal excretion as unchanged active substance. † 35% of administered dose. ‡ Prolonged in patients with impaired renal function. The Mean half-life 5 – 9 h (young) 12 – 18 h information in this table is based on the SmPC for apixaban, rivaroxaban, dabigatran and edoxaban. 12 h 10 – 14 h (patients) ‡ (t 1/2 ) 11 – 13 h (elderly) Please refer to the SmPC for further information. NOAC: non-vitamin K antagonist oral anticoagulant. T max 3 – 4 h 2 – 4 h 0.5 – 2 h 1 – 2 h 1. Ansell. Hematology Am Soc Hematol Educ Program. 2010:221 – 228; 2. Apixaban SmPC. Available at http://www.medicines.org.uk; 3. Rivaroxaban SmPC. Available at http://www.medicines.org.uk; 4. Dabigatran SmPC. Available at http://www.medicines.org.uk; 5. Edoxaban SmPC. Available at http://www.medicines.org.uk.

eal-world analysis 1 An in independent, retr trospective USA rea  The effectiveness and safety of apixaban, dabigatran, and rivaroxaban were compared for stroke prevention in NVAF patients, in the largest USA contemporary evaluation comparing NOACs and warfarin to date Three matched cohorts using 1:1 propensity score matching vs warfarin Analysis Non-interventional retrospective analysis using Rivaroxaban vs warfarin • Cox proportional hazards regression was used to administrative claims from Optumlabs Data compare outcomes in each of the propensity n = 32,350 Warehouse database and Medicare Advantage score matched cohorts Study population Study endpoints • Adult patients prescribed oral anticoagulants • Primary effectiveness outcome: stroke or systemic from 1 October 2010 – 30 June 2015* Dabigatran vs warfarin embolism, including ischaemic stroke, • All patients were required to have at least one haemorrhagic stroke, and systemic embolism. n = 28,614 inpatient or outpatient AF diagnosis at either • Primary safety outcome: major bleeding, primary or secondary positions (ICD-9 including gastrointestinal bleeding, intracranial diagnosis code 427.31) on the index date or at bleeding, and bleeding from other sites. baseline The definitions of efficacy and safety endpoints in the Apixaban vs warfarin ARISTOTLE, RE-LY and ROCKET-AF clinical trials differed to those in the USA real-world analysis. n = 15,390 *The USA real-world analysis did not include edoxaban, as it was not yet FDA approved during the time periods analysed There are no head-to-head clinical trials comparing the NOACs, so it is not appropriate to compare the results for different products across clinical trials, as trials have different designs and can vary greatly in terms of key parameters, e.g. patient populations. FDA: Food and Drug Administration; ICD: International Classification of Diseases; NOAC: non-VKA oral anticoagulant; NVAF: non -valvular atrial fibrillation. 1. Yao et al. J Am Heart Assoc . 2016;5:e003725.

NIC ICE Cli linical Guid ideli line 182 rec ecommendations for r ith CKD and NVAF 1 anticoagulants in in patients wit Anti ticoagulants • The NICE Clinical Guideline 182 recommendations for anticoagulant therapy in patients with CKD and NVAF is as follows: • Consider apixaban in preference to warfarin in people with a confirmed eGFR of 30 – 50 mL/min/1.73 m 2 and non-valvular atrial fibrillation who have one or more of the following risk factors: • Prior stroke or transient ischaemic attack • Age ≥75 years • Hypertension • Diabetes mellitus • Symptomatic heart failure CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; NICE: National Institute of Health and Care Excellence; NVAF, non-valvular atrial fibrillation. 1. NICE guidelines (CG182). Chronic kidney disease (partial update). Early identification and management of of chronic kidney disease in adults in primary and secondary care. July 2014.